Ubiquinone (2,3-dimethoxy-5-methyl-6-multiprenyl-1,4-benzoquinone, C59H90O4, 863.34 g/mol), also known as Co-EnzymeQ10 or shortly CoQ10, is of particular importance for nearly all living cells due to its antioxidative properties. CoQ10 is present in most aerobic microorganisms and in all animals, and CoQ10 is essential also for the human organism.
In the unstressed human organism, the reduced form of CoQ10, namely ubiquinol (2,3-dimethoxy-5-methyl-6-multiprenyl-1,4-hydroquinone, C59H92O4, 865.36 g/mol), also called CoQH2, is predominant.
Ubiquinol accounts for more than 80% of the total CoQ10 content in the human plasma and is thus an important plasma antioxidant for lipoproteins. Ubiquinol inhibits the oxidation of proteins and lipids in cell membranes and protects against lipid peroxidation and oxidative DNA degeneration, but also against other harmful molecules. Oxidative stress of all types, in particular caused by inflammation, can results in cell death. In his treatise “Schlüssel zur Mitochondrialen Medizin” F. H. Enzmann has indicated that the proportion of the oxidized form of CoQ10 to the reduced form of CoQH2 is 10:90. According to other authors, this ratio can vary between 10:30 and 10:90.
Morré and Morré (Morré, D. M., Guo, F. and Morré, D. J. An aging-related cell surface NADH oxidase (arNOX) generates superoxide and is inhibited by coenzyme CoQ10. Mol. Cell. Biochem. 264:101-109) describe a special source of extracellular ROS that they called “age-related NADH oxidase” or “arNOX proteins”. Studies have shown that ubiquinone (CoQ10) which is applied onto the skin penetrates into the layers of the epidermis where it reduces the oxidation degree and inhibits the arNOX activity, respectively. In contrast, CoQH2 and the molecules CoQ0, CoQ2, CoQ4, CoQ6, and CoQ7 showed no such effect. It could be shown that the inhibition can be attributed exclusively to the side chain of CoQ10 (n-decaprenol).
WO 2009/055951 describes a method for increasing the Co-Enzyme-Q10 content in phototrophic microorganisms that were cultivated in a culture medium in a bioreactor under standard conditions, with the growth of said microorganisms showing an exponential and a stationary growth phase. In said patent document, microalgae selected from the divisions Rhodophyta, Chlorophyta and Haptophyta, particularly Porphyridium purpureum, Chlorella vulgaris, Pavlova lutheri or Cricosphaera carterae, are mentioned as useful phototrophic microorganisms. The method described in WO 2009/055951 comprises as an essential step the induction of oxidative stress by co-incubation of stress-inducing substances and/or by increasing the surface radiation strength at the bioreactor. Alternatively or additionally, this can be achieved by adding oleate to the culture medium.
As an appropriate measure for inducting oxidative stress, it is proposed in WO 2009/055951 to carry out, particularly at the end of the exponential growth phase, a co-incubation of 13S-hydroperoxy-9Z,11 E-octadecadienoic acid and bivalent iron (Fe(II) and Fe2+ respectively) with the microorganisms in the culture medium.
Considering the known advantageous effects of CoQ10, which are also described particularly in WO 2009/055951, there is still a clear need for further improvement of the methods for producing CoQ10 and CoQH2.
It is conceivable that a further increase of the CoQ10 and CoQH2 content could be achieved by means of genetically modified algae. However, the use of such microorganisms is not devoid of problems, and, moreover, the bioavailability and the efficacy of such an approach would first have to be determined under the present quality standards.